The overall objectives of the proposed research is to define and characterize the molecular mechanisms underlying genetically-determined resistance and susceptibility in snails, biomphalaria glabrata, to infection by larval Schistosoma mansoni, causative agent of human schistosomiasis mansoni. Genetically-defined susceptible (PR albino) and refractory (10-R2) stocks of B. glabrata will be employed in comparative immunological and biochemical studies designed to provide an in-depth analysis of the three major interacting components involved in the immune association between S. mansoni and its snail host: the circulating hemocyte, soluble hemolymph components, and the schistosome tegumental surface. Specifically, monoclonal antibody and lectin probe techniques, in conjunction with in vitro cultivation methods will be employed (1) to identify and characterize molecularly distinct hemocyte populations and assess their impact on schistosome immune interactions, (2) to analyze and compare hemolymph constitutents from susceptible and refractory B. glabrata, and assess the role of isolated components in mediating parasite recognition and host cell reactivity, (3) to analyze the antigenic composition of the larval schistosome surface with emphasis on the possible involvement of shared or acquired host antigens in determining immune compatibility, (4) to determine the mechanism(s) of snail hemocyte cytotoxic killing of schistosome sporocysts in vitro, and (5) to assess the relative importance of cellular and humoral components in mediating immune reactions to schistosome larvae in vivo using adoptive transfer methods.